Immunotherapy in Acute Myeloid Leukemia: A Literature Review of Emerging Strategies

Abstract

In the last twenty years, we have witnessed a paradigm shift in the treatment and prognosis of acute myeloid leukemia (AML), thanks to the introduction of new efficient drugs or approaches to refine old therapies, such as Gemtuzumab Ozogamicin, CPX 3-5-1, hypomethylating agents, and Venetoclax, the optimization of conditioning regimens in allogeneic hematopoietic stem cell transplantation and the improvement of supportive care. However, the long-term survival of non-M3 and non-core binding factor-AML is still dismal. For this reason, the expectations for the recently developed immunotherapies, such as antibody-based therapy, checkpoint inhibitors, and chimeric antigen receptor strategies, successfully tested in other hematologic malignancies, were very high. The inherent characteristics of AML blasts hampered the development of these treatments, and the path of immunotherapy in AML has been bumpy. Herein, we provide a detailed review of potential antigenic targets, available data from pre-clinical and clinical trials, and future directions of immunotherapies in AML.

CSRP1 gene: a potential novel prognostic marker in acute myeloid leukemia with implications for immune response

“…We explored the correlation of CSRP1 with immune checkpoint genes and observed associations with eight immune checkpoint genes (TNFSF18: R = 0.30, CD244: R = − 0.30, CD40: R = 0.38, TNFRSF8: R = 0.36, CD80: R = 0.27, CD200R1: R = 0.35, CD276: R = 0.43, LAG3: R = 0.27). Described in a study, the CTLA4/CD80-86 Pathway, CD200/CD200R, LAG3, and CD276 have been identified or tested as promising targets in AML [ 34 ]. The alterations in these CSRP1-related genes may form a complex network affecting the immune response in AML patients at the genetic level, contributing to differential sensitivity to immunotherapies.…”

Therapy-Related Myeloid Neoplasm: Biology and Mechanistic Aspects of Malignant Progression

“…The management of t-MN and, in particular, TP53-mutated MN is still an unmet medical need. Nevertheless, the growing number of possible therapeutic targets [124], alongside the broader accessibility to HSCT, hold the promise of significant improvements in the near future. In particular, considering the overlapping mutational features between de novo and t-MN and the profound difference in the leukemic niche and in the staminal senescent mechanisms, the latter mechanism could be a promising target for senolytic agents which, alone or combined with chemotherapy, showed high efficacy in preclinical models [64,125].…”